While previous in vitro studies uncovered that the selective pressure provided by PARP inhibitors can lead to restoration of HR via revertant mutations in BRCA1/2 or RAD51C/D, inactivation of 53BP1 or REV7, and loss of PARP1 expression30, the importance of PARP1 mutations has only recently emerged based on forward genetic screens and the observation of a p.R591C variant in the PARP1 tryptophan-glycine-arginine-rich domain in an ovarian cancer patient who showed de novo resistance to olaparib20. The gene discussed is MAD2L2; the disease is ovarian cancer.